The prevalence of metabolic-associated fatty liver disease (MAFLD), detected by transient elastography, is alarmingly high among adolescents, researchers report in the February issue of Clinical Gastroenterology and Hepatology. Effective noninvasive strategies are needed to differentiate simple steatosis from progressive forms are urgently needed.
With the increasing prevalence of obesity, MAFLD has become the most common cause of chronic liver disease and abnormal liver enzymes in children and adolescents in Western countries. MAFLD varies in degrees of severity, from simple steatosis to steatohepatitis, with different degrees of fibrosis, and cirrhosis reported in even pediatric populations. Significant fibrosis predicts development of advanced liver disease and liver-related mortality, but little is known about the prevalence of MAFLD in pediatric populations.
Stefano Ciardullo et al estimated the prevalence of MAFLD and significant (≥F2) fibrosis by transient elastography in adolescents (12–18 years old) in the United States using data from the National Health and Nutrition Examination Survey 2017–2018 (data available from 867 adolescents; mean age, 15.1 years, 52% male, approximately 20% obese). A median controlled attenuation parameter (CAP) score ≥248 dB/m was used to identify adolescents any steatosis and a CAP ≥280 dB/m identified adolescents with S3 steatosis. A cutoff of median liver stiffness of 7.4 kPa was used to identify subjects with significant (≥F2) fibrosis.
Ciardullo et al found that 240 adolescents (24.16%) had any degree of steatosis (CAP≥248 dBm), 123 adolescents (11.6%) had S3 steatosis (CAP≥280 dBm), and 51 adolescents (4.4%) had significant fibrosis (liver stiffness ≥7.4 kPa).
A higher proportion of adolescents with steatosis was male (61.8% vs 50.5% without steatosis; P = .02), obese (91.5% in either the overweight or obese range), and Hispanic (45.2% vs 20.4% without steatosis; P < .01). Adolescents with steatosis also had a worse metabolic profile, characterized by lower high-density lipoprotein, higher triglyceride levels, and a higher prevalence of prediabetes and diabetes. Levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyltranspeptidase were higher in kids with CAP ≥280 dB/m. Nonetheless, only 41.4% of these adolescents had increased levels of ALT and 1.5% had a value ≥80 UI/L.
Multivariate analyses revealed that body mass index (odds ratio [OR] per unit increase, 1.2; 95% CI, 1.2–1.4), sex (OR female vs male participants , 0.5; 95% CI, 0.4–0.7), ethnicity (OR, Hispanic vs non-Hispanic white, 4.5; 95% CI, 1.7–11.8), and hypertension (OR, 3.5; 95% CI, 1.3–9.9) were associated with S3 steatosis, whereas body mass index (OR, 1.1 per unit increase; 95% CI, 1.0–1.2) and ethnicity (OR, non-Hispanic black vs non-Hispanic white, 3.9; 95% CI, 1.2–13.2) were associated with significant fibrosis.
A higher proportion of adolescents with significant fibrosis was obese (58.8% vs 19.5% without significant fibrosis; P < .01). Adolescents with significant fibrosis had a higher waist circumference, even though 35% were in the normal weight category.
In an evaluation of noninvasive serum-based markers of fibrosis, were applied, most adolescents fell in the low-risk group (99.25% with a value <1.3), NAFLD fibrosis score (99.97% with a value <–1.455), and AST-to-platelet ratio index (98.77% with a value <0.5); no participants were classified as having high risk of advanced fibrosis. However, 11.62% of the adolescents had a pediatric NAFLD fibrosis index value ≥9 (indicative of significant fibrosis) (95% CI, 9.85%–13.38%).
Ciardullo et al claim that this is the first study to estimate of the prevalence of MAFLD and significant fibrosis in adolescents from the general US population based on transient elastography data. The authors found that approximately 1 in 10 adolescents had a CAP ≥280 dB/m (indicating S3 steatosis), and almost 1 in 20 had evidence of increased liver stiffness, indicating significant fibrosis.
Although simple steatosis is considered to be benign, when significant fibrosis develops, risk of liver-related complications and mortality increase. Noninvasive methods are needed to identify adolescents with significant fibrosis; serum markers do not seem to perform well in this age group. On the other hand, transient elastography seems to be a promising technique in this target population. An separate article in the February issue of CGH reports that vibration-controlled transient elastography (VCTE), a non-invasive tool for detecting hepatic steatosis and fibrosis, accurately detects hepatic steatosis and fibrosis in recipients of liver transplants.
Ciardullo et al point out that a high proportion of adolescents with fibrosis are in the normal weight category and have ALT levels within the normal range. The authors warn that screening based on the presence of obesity and increased ALT levels is likely to miss a significant proportion of subjects with fibrosis.
The authors state that because steatohepatitis in adolescents seems to have a more severe course than in adults, MAFLD-related cirrhosis is likely to increase. Screening adolescents with transient elastography might help identify those that should be carefully followed or enrolled in clinical trials. More frequent visits and counseling on nutrition and physical activity are associated with better outcomes of obesity in children, and might contribute to successful treatment of MAFLD treatment.